The symptoms of allergic diseases, such as allergic rhinitis (hay fever) and allergic asthma, can be caused by a variety of atopic allergens, such as grasses, trees, weeds, animal dander, insects, molds, drugs and chemicals. These allergic diseases are mediated by an antibody known as immunoglobulin E, or simply IgE. Anti-IgE medicines that reduce IgE levels are attractive treatments for allergy patients.
IgE bonds to mast cells and basophils. Upon combination of a specific allergen with IgE bound to mast cells or basophils, the IgE may be crosslinked on the cell surface, resulting in the physiological effects of IgE-antigen interaction. This may result in the release of histamine, serotonin, heparin, a chemotactic factor for eosinoplylic leukocytes and/or the leukotrienes, C4, D4 and E4, which cause prolonged constriction of bronchial smooth muscle cells. These released substances are the mediators which result in allergic symptoms.
Vitamin B.sub.12 is essential to cell growth, cell reproduction, hematopoiesis, DNA synthesis and nucleoprotein synthesis. Deficiencies in Vitamin B.sub.12 or folic acid can lead to the inhibition of normal cell division and abnormal maturation and functioning of cells produced. These changes are most apparent in cells that undergo rapid mitosis (cell division), but all dividing cells are affected to some degree. In patients with Vitamin B.sub.12 or folic acid deficiency, pancytopenia (diminished production of red blood cells, white blood cells and platelets) may occur. The U.S. Food and Drug Administration (FDA) recognized the description of this problem on the molecular level in its approval of B.sub.12 for anemia.
The mechanism of action for Vitamin B.sub.12 in IgE-mediated allergic diseases, such as allergic rhinitis and asthma, may involve the maturation of certain immune system cells including polynucleated cells, natural killer (NK) cells, and CD8+ cells. The CD8+ cell is an immune system T lymphocyte believed to "put the brakes on" the immune system, making the allergy patient less sensitive to allergens such as pollen, cats, and mold. Typically, allergic individuals have numbers of the CD8+ suppressor cells that are low relative to CD4 aggressor cells. These immune system cells may require a sustained and elevated serum Vitamin B.sub.12 concentration to develop from an immature state to a mature state in which they can exert their down-regulatory function on the immune system. Polynucleated cells are known to have memories that last many years, a concept consistent with controlled studies demonstrating reductions in symptoms and in specific IgE levels persisting many months after parenteral Vitamin B.sub.12 treatment.
When Vitamin B.sub.12 is delivered parenterally, it passes into the circulation for distribution throughout the body before arriving at the liver. It is during this first pass in its native form that it is believed to exert its therapeutic effect.
Studies indicate that ingested oral cyanocobalamin is ineffective in the treatment of allergic disease, perhaps because once ingested, it goes directly to the liver where it metabolized. The ineffectiveness may also be caused by poor absorption. Gastrointestinal absorption of Vitamin B.sub.12 depends on the presence of sufficient intrinsic factor and calcium ions. Its absorption may be hindered by the presence of large amounts of Vitamin C. Tens of millions of people have diets rich in Vitamin B.sub.12 (from animal products or supplements) and continue to suffer from allergic rhinitis and/or asthma.
Cyanocobalamin is the most widely sold analogue of Vitamin B.sub.12, with other similar molecules also available. Cyanocobalamin is found in injectable and oral modes of delivery, and has the advantage over other types of B.sub.12 of having a stable shelf life at standard temperature and pressure (STP).
The analogues of Vitamin B.sub.12 are the only molecules used by the human body that contain cobalt. The empirical formula of cyanocobalamin is: C.sub.63 H.sub.88 CoN.sub.14 O.sub.14 P.
U.S. Pat. No. 5,135,918, which is owned by the applicant, Allergy Limited LLC, discloses a highly effective method of achieving long term relief from the symptoms of atopic allergy by repeated subcutaneous and/or intramuscular injections of B.sub.12 over a short period of time. In practice, the treatment has comprised thirty injections of B.sub.12, preferably cyanocobalamin, administered twice daily over a period of fifteen days. This series of 30-injections has been successful from a point of view of efficacy in treating allergic disease, but has resulted in subjects reporting bruising and/or soreness at the local injection site. The difficulties involved in having the patient go into a medical clinic 30 times over a fifteen-day period for injections are numerous. However, providing patients with syringes for self-injection also poses problems. Once a syringe has been used it is contaminated and must be disposed of in a biohazard container or there is risk of transmitting diseases such as hepatitis or the HIV virus. Concerns have been raised about the possibility of cross-contamination of vials by lay allergy patients with minimal medical knowledge who self-inject. Both the manufacture and disposal of syringes are environmentally hazardous.